Neural precursor cells as a novel target for interferon-beta.
The immunomodulating agent interferon-beta (IFNbeta) is administered therapeutically in several autoimmune diseases and endogenously released by immune cells during diverse infections. As in recent years a variety of pro- and anti-inflammatory substances were shown to influence significantly neural precursor cells that are implicated in a variety of regenerative mechanisms but also in tumor growth, we studied a possible effect of IFNbeta on neural precursor cells derived from murine embryonic day 14 neurospheres. First, we demonstrated that interferon type-I receptors are expressed on neural precursor cells and that these cells respond to IFNbeta treatment by up-regulating IFNbeta inducible genes including Myxovirus 1 and viperin. Furthermore, we could show for the first time that IFNbeta treatment significantly inhibited the proliferation of neural precursor cells possibly through induction of p21, a cyclin-dependent kinase inhibitor. IFNbeta did not exert cytotoxic or neuroprotective effects and we could not see effects on the differentiation of neural precursor cells into total amounts of neurons, astrocytes or oligodendrocytes. However, we found that IFNbeta markedly diminished neurite outgrowth and neuronal maturation of neural precursor-derived neurons.
Wellen
Jennifer
J
Department of Neurology, Heinrich-Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany.
Walter
Janine
J
Jangouk
Parastoo
P
Hartung
Hans-Peter
HP
Dihné
Marcel
M
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
D007155:Immunologic Factors; D009419:Nerve Tissue Proteins; D017471:Receptors, Interferon; D013778:Tetrazolium Salts; D013844:Thiazoles; D016899:Interferon-beta; D053148:Caspase 3; C022616:thiazolyl blue